1. Impaired growth and force production in skeletal muscles of young partially pancreatectomized rats: a model of adolescent type 1 diabetic myopathy?
- Author
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Gordon CS, Serino AS, Krause MP, Campbell JE, Cafarelli E, Adegoke OA, Hawke TJ, and Riddell MC
- Subjects
- Adolescent, Analgesics pharmacology, Animals, Diabetes Mellitus, Type 1 complications, Disease Models, Animal, Humans, Ketamine pharmacology, Male, Muscle Fatigue drug effects, Muscle Fatigue physiology, Muscle Fibers, Skeletal drug effects, Muscle Fibers, Skeletal physiology, Muscle, Skeletal drug effects, Muscle, Skeletal metabolism, Muscular Diseases etiology, Random Allocation, Rats, Rats, Sprague-Dawley, Signal Transduction, Succinate Dehydrogenase metabolism, TOR Serine-Threonine Kinases metabolism, Ubiquitination, Xylazine pharmacology, Diabetes Mellitus, Type 1 physiopathology, Muscle, Skeletal physiopathology, Muscular Diseases physiopathology, Pancreatectomy methods
- Abstract
This present study investigated the temporal effects of type 1 diabetes mellitus (T1DM) on adolescent skeletal muscle growth, morphology and contractile properties using a 90% partial pancreatecomy (Px) model of the disease. Four week-old male Sprague-Dawley rats were randomly assigned to Px (n = 25) or Sham (n = 24) surgery groups and euthanized at 4 or 8 weeks following an in situ assessment of muscle force production. Compared to Shams, Px were hyperglycemic (>15 mM) and displayed attenuated body mass gains by days 2 and 4, respectively (both P<0.05). Absolute maximal force production of the gastrocnemius plantaris soleus complex (GPS) was 30% and 50% lower in Px vs. Shams at 4 and 8 weeks, respectively (P<0.01). GP mass was 35% lower in Px vs Shams at 4 weeks (1.24±0.06 g vs. 1.93±0.03 g, P<0.05) and 45% lower at 8 weeks (1.57±0.12 vs. 2.80±0.06, P<0.05). GP fiber area was 15-20% lower in Px vs. Shams at 4 weeks in all fiber types. At 8 weeks, GP type I and II fiber areas were ∼25% and 40% less, respectively, in Px vs. Shams (group by fiber type interactions, P<0.05). Phosphorylation states of 4E-BP1 and S6K1 following leucine gavage increased 2.0- and 3.5-fold, respectively, in Shams but not in Px. Px rats also had impaired rates of muscle protein synthesis in the basal state and in response to gavage. Taken together, these data indicate that exposure of growing skeletal muscle to uncontrolled T1DM significantly impairs muscle growth and function largely as a result of impaired protein synthesis in type II fibers.
- Published
- 2010
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